McDonald Criteria For Multiple Sclerosis Research Articles

Radiologically isolated syndrome is antiquated amidst evolving McDonald criteria for multiple sclerosis - ERRATUM.

Radiologically isolated syndrome is antiquated amidst evolving McDonald criteria for multiple sclerosis - ERRATUM.

Optic Nerve Involvement and Diagnosing Multiple Sclerosis

The 2017 McDonald criteria for multiple sclerosis (MS) diagnosis do not include the optic nerve as a site for dissemination in space (DIS).

K Index is a Reliable Marker of Intrathecal Synthesis, and an Alternative to IgG Index in Multiple Sclerosis Diagnostic Work-Up.

The K free light chain (K) index has been suggested as a reliable marker of intrathecal synthesis, despite the 2017 McDonald criteria for multiple sclerosis (MS) suggesting to “interpret with caution positive immunoglobulin G (IgG) index when testing for oligoclonal bands (OB) is negative or not performed”. The aim of this study was to compare the performance of K and IgG indexes for MS diagnosis and OB detection in a cohort of Italian patients. We enrolled 385 patients (127 MS, 258 non-MS) who had cerebrospinal fluid (CSF) analysis, including isoelectric focusing (IEF), to detect OB in the diagnostic work-up. Albumin, IgG and free light chains were measured by nephelometry and used to calculate IgG and K indexes. Although the two markers were highly related (r = 0.75, r2 = 0.55, p < 0.0001), the K index showed greater sensitivity and negative predictive value (versus the IgG index) for OB detection (97% versus 48% and 97% versus 71%) and MS diagnosis (96% versus 50% and 98% versus 78%). These results support K index (and not IgG index) as a first-line marker for MS, followed by IEF, according to a sequential testing approach in CSF analysis.

2017 McDonald criteria for multiple sclerosis: Earlier diagnosis with reduced specificity?

BackgroundMcDonald criteria for multiple sclerosis (MS) diagnosis were revised in 2017. ObjectiveAim of our study was to evaluate and compare the sensitivity and specificity of 2017 and 2010 McDonald criteria in patients presenting with an initial demyelinating event (IDE). MethodsWe retrospectively identified patients with an IDE and collected clinical, MRI and CSF data in order to demonstrate fulfilment of 2010 and 2017 McDonald criteria. Results2017 McDonald criteria showed 100% (86.8–100%) sensitivity and 13.8% (3.9–31.7%) specificity. Conclusion2017 McDonald criteria appear to have higher sensitivity but reduced specificity compared to 2010 McDonald criteria.

Application of the 2017 Revised McDonald Criteria for Multiple Sclerosis to Patients With a Typical Clinically Isolated Syndrome

In 2017, the International Panel on Diagnosis of Multiple Sclerosis revised the McDonald 2010 criteria for the diagnosis of multiple sclerosis (MS). The new criteria are easier to apply and could lead to more and earlier diagnoses. It is important to validate these criteria globally for their accuracy in clinical practice. To evaluate the diagnostic accuracy of the 2017 criteria vs the 2010 criteria in prediction of clinically definite MS in patients with a typical clinically isolated syndrome (CIS). A total of 251 patients at Erasmus MC, Rotterdam, the Netherlands, in collaboration with several regional hospitals, fulfilled the inclusion criteria. Thirteen patients received another diagnosis early in the diagnostic process and therefore were excluded from the analyses. Nine patients with CIS declined to participate in the study. This left 229 patients who were included between March 2006 and August 2016 in this prospective CIS cohort. Patients underwent a baseline magnetic resonance imaging scan within 3 months after onset of symptoms and, if clinically required, a lumbar puncture was performed. Data were analyzed between December 2017 and January 2018. Sensitivity, specificity, accuracy, and positive and negative predictive value were calculated after 1, 3, and 5 years for the 2017 vs the 2010 criteria. Among the 229 patients with CIS, 167 were women (73%), and the mean (SD) age was 33.5 (8.2) years. One hundred thirteen patients (49%) were diagnosed as having CDMS during a mean (SD) follow-up time of 65.3 (30.9) months. Sensitivity for the 2017 criteria was higher than for the 2010 criteria (68%; 95% CI, 57%-77% vs 36%; 95% CI, 27%-47%; P < .001), but specificity was lower (61%; 95% CI, 50%-71% vs 85%; 95% CI, 76%-92%; P < .001). Using the 2017 criteria, more MS diagnoses could be made at baseline (n = 97 [54%]; 95% CI, 47%-61% vs n = 46 [26%]; 95% CI, 20%-32%; P < .001). In the group with at least 5 years of follow-up, 33% of patients who were diagnosed as having MS using the 2017 criteria did not experience a second attack during follow-up vs 23% when using the 2010 criteria. The 2017 revised McDonald criteria are associated with greater sensitivity but less specificity for a second attack than the previous 2010 criteria. The tradeoff is that it leads to a higher number of MS diagnoses in patients with a less active disease course.

Application of the 2017 McDonald diagnostic criteria for multiple sclerosis in Korean patients with clinically isolated syndrome

Objectives: To evaluate the validity of the revised 2017 McDonald criteria for multiple sclerosis (MS) compared with the 2010 McDonald criteria to predict conversion to clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndrome (CIS). Methods: A total of 163 patients from seven referral hospitals in Korea, who experienced a first clinical event suggestive of MS between 2006 and 2017, were enrolled. Patients were stratified into two groups according to outcome at the last visit: CDMS converters who experienced a second clinical event and non-converters. Results: Of the 163 patients with a mean follow-up of 63 months, 60% converted to CDMS. The sensitivity, specificity, positive and negative predictive values and accuracy were, respectively, 88.8%, 43.1%, 70.2%, 71.8% and 70.6% for the 2017 McDonald criteria and 53.1%, 69.2%, 72.2%, 49.5% and 59.5% for the 2010 McDonald criteria. After exclusion of 82 patients who received disease-modifying agents before the second attack, the specificity of the 2017 and 2010 McDonald criteria increased to 85.0% and 95.0%, but sensitivity decreased to 83.6% and 47.5%, respectively. Conclusion: The 2017 McDonald criteria afforded higher sensitivity and accuracy but lower specificity compared with the 2010 McDonald criteria for prediction of conversion to CDMS in Korean CIS patients.

MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 2: Epidemiology, clinical presentation, radiological and laboratory features, treatment responses, and long-term outcome.

BackgroundA subset of patients with neuromyelitis optica spectrum disorders (NMOSD) has been shown to be seropositive for myelin oligodendrocyte glycoprotein antibodies (MOG-IgG).ObjectiveTo describe the epidemiological, clinical, radiological, cerebrospinal fluid (CSF), and electrophysiological features of a large cohort of MOG-IgG-positive patients with optic neuritis (ON) and/or myelitis (n = 50) as well as attack and long-term treatment outcomes.MethodsRetrospective multicenter study.ResultsThe sex ratio was 1:2.8 (m:f). Median age at onset was 31 years (range 6-70). The disease followed a multiphasic course in 80 % (median time-to-first-relapse 5 months; annualized relapse rate 0.92) and resulted in significant disability in 40 % (mean follow-up 75 ± 46.5 months), with severe visual impairment or functional blindness (36 %) and markedly impaired ambulation due to paresis or ataxia (25 %) as the most common long-term sequelae. Functional blindess in one or both eyes was noted during at least one ON attack in around 70 %. Perioptic enhancement was present in several patients. Besides acute tetra-/paraparesis, dysesthesia and pain were common in acute myelitis (70 %). Longitudinally extensive spinal cord lesions were frequent, but short lesions occurred at least once in 44 %. Fourty-one percent had a history of simultaneous ON and myelitis. Clinical or radiological involvement of the brain, brainstem, or cerebellum was present in 50 %; extra-opticospinal symptoms included intractable nausea and vomiting and respiratory insufficiency (fatal in one). CSF pleocytosis (partly neutrophilic) was present in 70 %, oligoclonal bands in only 13 %, and blood-CSF-barrier dysfunction in 32 %. Intravenous methylprednisolone (IVMP) and long-term immunosuppression were often effective; however, treatment failure leading to rapid accumulation of disability was noted in many patients as well as flare-ups after steroid withdrawal. Full recovery was achieved by plasma exchange in some cases, including after IVMP failure. Breakthrough attacks under azathioprine were linked to the drug-specific latency period and a lack of cotreatment with oral steroids. Methotrexate was effective in 5/6 patients. Interferon-beta was associated with ongoing or increasing disease activity. Rituximab and ofatumumab were effective in some patients. However, treatment with rituximab was followed by early relapses in several cases; end-of-dose relapses occurred 9-12 months after the first infusion. Coexisting autoimmunity was rare (9 %). Wingerchuk’s 2006 and 2015 criteria for NMO(SD) and Barkhof and McDonald criteria for multiple sclerosis (MS) were met by 28 %, 32 %, 15 %, 33 %, respectively; MS had been suspected in 36 %. Disease onset or relapses were preceded by infection, vaccination, or pregnancy/delivery in several cases.ConclusionOur findings from a predominantly Caucasian cohort strongly argue against the concept of MOG-IgG denoting a mild and usually monophasic variant of NMOSD. The predominantly relapsing and often severe disease course and the short median time to second attack support the use of prophylactic long-term treatments in patients with MOG-IgG-positive ON and/or myelitis.

Biopsy-Supported Tumefactive Demyelination of the Central Nervous System in Children.

Pediatric tumefactive lesions remains challenging to clinicians in terms of diagnosis and treatment. The authors describe 11 children with biopsy-proven central nervous system tumefactive demyelination. The mean age of onset was 11 years. Clinical and radiological data coupled with biopsy aided in the diagnosis of tumefactive demyelination. Of the 6 cases in which oligoclonal band data were available, only 3 showed oligoclonal band in the cerebrospinal fluid. Due to poor recovery despite treatment with high-dose glucocorticosteroids, intravenous immunoglobulin, and/or plasmapheresis, 6 cases went on to receive cyclophosphamide with marked improvement. Long-term data were available on 9 cases. Eight of 9 cases were started on preventative multiple sclerosis therapy after initial presentation; 1 is pending discussion with family. Five of the 8 cases had clinical relapse during treatment. Seven cases met 2010 McDonald criteria for multiple sclerosis at follow-up, (1 developed secondary progressive multiple sclerosis), and 2 cases remained as clinically isolated syndrome on treatment.

Occurrence and long-term outcome of tumefactive demyelinating lesions in multiple sclerosis.

Although tumefactive multiple sclerosis is a well recognized variant of multiple sclerosis, prognostic uncertainty still exists about long term prognosis. The aim of this study was to estimate the occurrence and long term outcome of tumefactive demyelinating lesions (TDLs) in a cohort of multiple sclerosis patients. We reviewed brain MRI of 443 patients referred to our MS clinic. All patients meeting the McDonald criteria for multiple sclerosis and showing at least one TDL were included. Kaplan-Meier estimates of disease-free survival in patient cohort were compared with control group without TDLs using a log-rank test. Seven cases with TDLs were identified (occurrence 1.58%). Tumefactive demyelinating lesion recurrence was 16.6%. Cumulative proportion of patients free from clinical relapse and from new T2 lesions was lower in the control group although not reaching statistical significance (30 vs 50%; P=0.666 and 21.7 vs 33.3%; P=0.761, respectively). Disability progression analysis showed a not significant trend towards lower probability of remaining progression free for TDL patients (50 vs 61%; P=0.295). Occurrence of tumefactive demyelinating lesions in our cohort was higher than those reported in other studies. Overall, TDLs were not predictive of poor outcome in terms of disability progression.

Combined central and peripheral demyelination: Clinical features, diagnostic findings, and treatment

Combined central and peripheral demyelination (CCPD) is rare, and current knowledge is based on case reports and small case series. The aim of our study was to describe the clinical features, diagnostic results, treatment and outcomes in a large cohort of patients with CCPD. Thirty-one patients entered this retrospective, observational, two-center study. In 20 patients (65%) CCPD presented, after an infection, as myeloradiculoneuropathy, encephalopathy, cranial neuropathy, length-dependent peripheral neuropathy, or pseudo-Guillain-Barré syndrome. Demyelinating features of peripheral nerve damage fulfilling European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) electrodiagnostic criteria for CIDP were found in 23 patients (74%), and spatial dissemination of demyelinating lesions on brain MRI fulfilling the 2010 McDonald criteria for multiple sclerosis (MS) in 11 (46%). Two thirds of the patients had a relapsing or progressive disease course, usually related to the appearance of new spinal cord lesions or worsening of the peripheral neuropathy, and showed unsatisfactory responses to high-dose corticosteroids and intravenous immunoglobulins. The clinical presentation of CCPD was severe in 22 patients (71%), who were left significantly disabled. Our data suggest that CCPD has heterogeneous features and shows frequent post-infectious onset, primary peripheral nervous system or central nervous system involvement, a monophasic or chronic disease course, inadequate response to treatments, and a generally poor outcome. We therefore conclude that the current diagnostic criteria for MS and CIDP may not fully encompass the spectrum of possible manifestations of CCPD, whose pathogenesis remains largely unknown.

Revised McDonald criteria for multiple sclerosis diagnostics in Central Russia: Sensitivity and specificity

Background: The 2010 revised McDonald criteria were developed with data gathered from Caucasian European and North American populations, and their applicability has been questioned for the Russian population. Objective: The objective of this report is to compare the specificity, accuracy, sensitivity and predictive value of MRI criteria incorporated to the new (2010) and old (2005) McDonald criteria for early multiple sclerosis (MS) diagnostics in the Nyzhnyi Novgorod (Russia) population. Methods: A total of 103 patients with symptoms suggestive of MS were recruited from 2008 to 2011 retrospectively. Patients were followed up until MS was confirmed or other proved diagnoses were determined. Their baseline and follow-up brain and spinal cord MRIs were retrospectively evaluated. Sixty-two patients (60%) converted to MS during the follow-up period (mean in 11±4.2 months). Results: In 41 cases (38%) diagnoses another than MS were established. The sensitivity, specificity, accuracy, PPV and NPV of the revised MRI criteria were 74%, 93%, 82%, 94%, 70%, respectively. Conclusions: Despite the limitations of our study, we conclude that the ability of the revised MRI criteria for early MS diagnostics in the Russian population is approximately similar to that determined by the international panel in Europe.

To tell or not to tell? Revealing the diagnosis in multiple sclerosis

We review briefly (1) the history of patient-physician relationship and its evolution from a physician-centered to patient-centered model; (2) the impact of the McDonald Criteria for Multiple Sclerosis (MS); (3) why it is important to tell patients of their diagnosis; (4) how physicians should disclose the diagnosis to patients; (5) dealing with suspected MS; and (6) prognosis and treatment. For the majority of clinically definite MS patients we advocate disclosure, identify steps for physicians to communicate the diagnosis and propose a framework to follow when revealing a diagnosis of MS.

Neuromyelitis optica-IgG testing in an Indian cohort with neuromyelitis optica and related demyelinating disorders: Our experience

Background:Neuromyelitis optica (NMO) is an immune-mediated inflammatory demyelinating disorder of the central nervous system with a predilection for the optic nerves and the spinal cord. Immunopathological evidence suggests that the target antigen of the disease is aquaporin-4. An IgG antibody against this protein has been explored as a molecular marker for the disease and as a diagnostic tool due to its high sensitivity and specificity in various populations.Objective:To assess the value of NMO-IgG testing in Indian patients with clinical and magnetic resonance imaging features consistent with NMO and longitudinally extensive transverse myelitis (LETM).Materials and Methods:Forty-five patients with clinical and magnetic resonance imaging features consistent with NMO, LETM, and MS were tested for serum NMO-IgG. Of these patients, 22 patients satisfied revised (2006) Wingerchuk criteria for NMO (excluding NMO-IgG status) and 11 patients had LETM. Twelve patients satisfied the revised (2010) McDonald criteria for multiple sclerosis (MS).Results:Of the 21 patients, satisfying the criteria for NMO and for whom the test results were available, 17 were positive for NMO-IgG (80.9%), and of the 11 patients having LETM, 6 (54.5%) were positive for NMO-IgG. In one patient with NMO, the test result was not available. None of the 12 patients satisfying McDonald criteria for MS showed NMO-IgG seropositivity.Conclusion:Our study suggests that it is worthwhile to pursue NMO-IgG testing as a diagnostic tool for patients with clinical and Magnetic Resonance Imaging (MRI) features consistent with NMO and LETM in the Indian population.

The Incidence of Clinically Isolated Syndrome Is Higher in African Americans and Whites Compared with Hispanics and Asians (P01.140)

Objective: To determine whether the incidence of clinically isolated syndrome (CIS) the precursor form of multiple sclerosis (MS) that encompasses optic neuritis and transverse myelitis as well as other clinical presentations, varies by race/ethnicity in a multi-ethnic, population-based cohort. Background We previously reported that the incidence of MS was higher in blacks than whites, Hispanics and Asians. Design/Methods: We used electronic record searches and complete medical records review to identify all newly diagnosed CIS and MS cases in the population-based, multiethnic membership of Southern California Kaiser Permanente (KPSC) between 2008 and 2009. The KPSC membership contributed 7,410,754 person-years of observation during the study period and the racial/ethnic distribution was 36.5% white, 8.6% black, 43.4% Hispanic, 9.3% Asian/Pacific Islanders (Asian/PI) and 1.9% other. Results: We identified 254 incident cases of CIS cases who did not yet met McDonald criteria for MS and did not have other obvious causes (e.g. viral, lupus, ischemia). The most common clinical presentation was optic neuritis (48.4%) followed by transverse myelitis (32.7%), other forms of mono-regional CIS (9.8%) and poly-regional CIS (9.1%). The average age at diagnosis with CIS was 42.9 years (range 14.8-80.8) and 70.5% were women. Among CIS cases, the racial/ethnic distribution was 47.6% white, 12.6% black, 33.1% Hispanic, 4.3% Asian/PI and 2.4% other. The incidence of CIS was 3.4 per 100,000 person-years. Incidence of CIS was higher in black (5.1, 95%CI=3.5-7.1) and white, non-Hispanic individuals (4.5, 95%CI=3.7-5.3) compared with white, Hispanic (2.6, 95%CI=2.1-3.2) and Asian/PI individuals (1.6, 95%CI=0.8-2.9; p Conclusions: The incidence of CIS is 3.4 per 100,000 person-years in a multi-ethnic, population-based cohort of Southern Californians. The incidence of CIS is higher in black and white individuals compared with Hispanic and Asian/PI individuals. Incidence rates standardized to the US census by age and gender will be presented at the meeting. Disclosure: Dr. Langer-Gould has nothing to disclose. Dr. Brara has nothing to disclose. Dr. Beaber has nothing to disclose. Dr. Zhang has nothing to disclose.

Spinal cord involvement in Balo's concentric sclerosis

We present a patient with a history of myelitis, who had a steroid refractory attack of CNS inflammatory demyelinating disease that developed into cerebral concentric sclerosis of Balo after plasma exchange. The acute inflammatory disease involved the spinal cord, a phenomenon rarely demonstrated. This patient fulfilled the McDonald criteria for multiple sclerosis. Plasmapheresis did not have a beneficial effect, but the patient stabilised at high EDSS after treatment with mitoxantron.

Selective magnetization transfer ratio decrease in the visual cortex following optic neuritis

Patients with clinically isolated syndromes suggestive of multiple sclerosis have evidence for abnormality in normal appearing grey matter detected using the magnetization transfer ratio (MTR), a quantitative MRI measure. One potential mechanism for the decreased grey matter MTR (GM MTR) observed is trans-synaptic morphological abnormality secondary to demyelinating lesions that are in an anatomically linked pathway but remote location. We investigated this potential association by studying the location of abnormalities using voxel-based analysis of GM MTR maps in a group of 80 patients studied within 6 months of presenting with isolated optic neuritis and compared the findings with those seen in 50 age- and sex-matched healthy controls. Occipital cortex and whole brain analysis comparing all optic neuritis patients and controls revealed a selective decrease of MTR bilaterally in the visual cortex in patients [Brodmann area (BA) 17]. Whole brain analysis of patients fulfilling the McDonald criteria for multiple sclerosis (n = 20) showed a lower MTR compared to controls bilaterally in the visual cortex (BA 17/18), left hippocampus, bilateral superior temporal gyrus, bilateral lenticular nuclei and the right cerebellum. There was no significant difference in the percentage of grey matter between patients and controls in the regions of abnormal MTR detected in the visual cortex. The intrinsic MTR decrease seen in patients suggests that there are structural changes in the visual cortex following an attack of optic neuritis. Potential mechanisms for this include trans-synaptic neuronal degeneration and cortical synaptic morphological changes; such abnormalities may also contribute to MTR abnormalities observed in the normal appearing grey matter in multiple sclerosis.

Elevated white matter myo-inositol in clinically isolated syndromes suggestive of multiple sclerosis.

Normal-appearing white matter (NAWM) in established multiple sclerosis has been shown to be abnormal using a variety of magnetic resonance (MR) techniques, including proton MR spectroscopy ((1)H-MRS), although the stage at which these changes first appear is less clear. Using a 1.5 T scanner and single-voxel (1)H-MRS [TR 3000 ms, TE 30 ms, point-resolved spectroscopy (PRESS) localization], we determined NAWM metabolite concentrations in 96 patients a mean of 19 weeks (range 12-28 weeks) after onset of a clinically isolated syndrome (CIS) suggestive of multiple sclerosis and in 44 healthy control subjects. Absolute concentrations of N-acetyl-aspartate, total creatine and phosphocreatine (Cr), choline-containing compounds, glutamate plus glutamine, and myo-inositol (Ins) were estimated automatically using the LCModel. Compared with control subjects, the concentration of Ins was elevated in CIS NAWM (mean 3.31 mM, SD 0.86 versus mean 3.82 mM, SD 1.06; P = 0.001). The increase in Ins was also seen in the patient subgroup with abnormal T2-weighted MRI (mean 3.88 mM, SD 1.10; P = 0.001) and in those who satisfied the McDonald criteria for multiple sclerosis (mean 4.04 mM, SD 1.31; P = 0.001). An increase in Cr was also observed in CIS NAWM (P = 0.023), but other metabolites did not significantly differ between the whole CIS group and control subjects. There was no significant correlation between NAWM Ins and T2 lesion load. The early increase in Ins may reflect a process of pathogenic importance in multiple sclerosis NAWM. Follow-up studies will investigate whether the increase in NAWM Ins is of prognostic importance for future relapses and disability.